The transplanted cells mature into neurons producing the neurotransmitter GABA. They then inhibit excessive neural activity that manifest as seizures. Progenitor cells are like stem cells, but have taken steps toward differentiating.

If this treatment can be applied to people, it would provide an alternative to surgery that attempts to control seizures by removing part of the brain, the study said.

In the study, adult mice were given the drug pilocarpine, inducing temporal lobe epilepsy, the most common form. The progenitor cells, taken from mouse embryos, were injected into the hippocampus of some of the mice, others used as controls did not get the cells. These cells matured in place in the treated mice after transplantation, showed evidence of function, and the mice stopped having seizures and restored impaired learning, the researchers said.

Most of the cells died after transplantation; only about 15 percent remained 60 days afterward. But the remaining cells were enough to confer "a substantial therapeutic effect on seizures and abnormal behaviors commonly associated with epilepsy," the study stated.

New inhibitory neurons in the dentate gyrus of a mouse with epilepsy that were generated by MGE progenitor cell grafts into hippocampus. Grafted neurons are shown in white; somatostatin-positive inhibitory neurons are shown in red.
— RF Hunt and SC Baraban

New inhibitory neurons in the dentate gyrus of a mouse with epilepsy that were generated by MGE progenitor cell grafts into hippocampus. Grafted neurons are shown in white; somatostatin-positive inhibitory neurons are shown in red.
/ RF Hunt and SC Baraban

The study's first author was Robert F. Hunt, and the senior author was Scott C. Baraban. Both are with the Epilepsy Research Laboratory at UC San Francisco.

The GABA-producing cells belong to a class of neurons called "interneurons" that regulate connections between neurons. They are neither motor nor sensory neurons. In some forms of epilepsy, these cells are destroyed or nonfunctional, so abnormal spikes of neuronal activity are not suppressed, resulting in seizures.

The study was funded by grants from the National Institute of Neurological Disorders and Stroke, an agency of the NIH, and the California Institute of Regenerative Medicine. It is titled: "GABA progenitor grafted into the adult epileptic brain control seizures and abnormal behavior."

Previously, the researchers had found that transplanting these cells would reduce seizures in mice with a specific mutation.

However, whether this approach would be successful in the more common and medically refractory types of epilepsy seen in adults has not been directly tested," the authors wrote in the Nature Neuroscience paper. "The emergence of epilepsy in adulthood involves a wide range of modifications to brain structure and function, and it is not known whether the adult nervous system can support GABA progenitor cell migration, differentiation, integration or functional recovery of pre-existing deficits."

The transplanted cells showed evidence of integrating into the hippocampal network, the paper said, and mice getting the transplants showed better performance than control mice in a water maze test, where the mice must locate a hidden underwater platform to escape.

"Interneuron-based cell transplantation might have an important clinical advantage over current therapeutic approaches in that cell grafts can be targeted to spatially restricted brain regions as a one-time procedure for seizure control," the paper said. "In addition to the obvious benefits for promoting functional recovery, this approach might also be useful for limiting adverse behavioral side effects that can be associated with medications or for sparing areas of the epileptic brain normally targeted for surgical resection."

A recent commentary by Hunt and Baraban examined a study that suggested embryonic stem cells would provide a good source for creating these GABA-producing progenitors. It highlighted the problems still facing work with embryonic stem cells:

"These include inefficient and uncontrolled differentiation of ES cells into mixed cell populations, a relatively slow course of differentiation and development in vivo, and the tendency for ES cells to form tumors after transplantation," Hunt and Baraban wrote.

For an overview of progress in epilepsy therapy, I spoke recently with Dr. Timothy Pedley, the new president of the American Academy of Neurology. Below is a video of that interview, taken in March: